Chlorpheniramine, sedative

Values are the means from six separate experiments. SE was less than 10% of the mean. Dose of test compounds, chlorpheniramine maleate and cetirizine are 10 mg/kg for antihistaminic activity, and 5 mg/kg for sedative-hypnotic activity... 

As sedation is one of the major side effects associated with antihistamines, the test compounds were also evaluated for their sedative potentials. This was determined by measuring the reduction in locomotor activity using an ac-tophotometer [6,7]. The test compounds and the reference standards (chlorpheniramine maleate and cetirizine) were administrated orally at a dose of 5 mg/kg in 1% CMC. 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

Although sedative antihistamines do not potentiate the effect of alcohol, they should be avoided in excess quantity. Overdose of astemizole can be treated with gastric lavage and supportive measures.86 Coadministration of astemizole and ter-fenadine with antiarrhythmics, antipsychotics, cisapride, and diuretics should be avoided. Chlorpheniramine maleate has been found to be incompatible with phe-nobarbitone sodium, kanamycin sulfate, and calcium chloride. Cyclizines have been used alone or with opioids in tablets or in injectable form for euphoric effects. Cyproheptadine has shown dependence in long-term use. Diphenhydramine is reported to be incompatible with amphotericin, cephalothin sodium, and hydrocortisone sodium succinate. Diphenhydramine and pheniramine maleate are sometimes used as drugs of abuse. Studies have shown that promethazine is adsorbed onto glass, plastic containers, and infusion systems.87... 

Chlorphenamine (chlorpheniramine) is a first-generation antihistamine, an alkylamine derivative, with sedative and antimuscarinic activity. 

Prototypical agent Diphenhydramine. Other first-generation antihistamines include chlorpheniramine, clemastine, promethazine, and cyproheptadine. Second-generation antihistamines— loratadine, cetirizine, and fexofenadine—were developed to circumvent anticholinergic and sedative side effects. 

The most common side effect of the antihistaminics is sedation, and all of them cause it to varying degrees. For example, diphenhydramine, dimenhydrinate, and promethazine cause marked sedation, but pyrilamine produces only moderate sedation. Chlorpheniramine, meclizine, and cyclizine have mild sedative properties, while terfenadine, astemizole, loratadine, and cetirizine are nonsedating. 

The sedative property which is so highly expressed in diphenhydramine existed in a less measure in other antihistamines. In an endeavour to lessen it, to help those who need medication at times when they must be alert, chlor-phenamine (9.57) (chlorpheniramine, Chlortrimeton ) was introduced. In this type, the second polar atom (N or O) has been eliminated from the aliphatic chain. The pAa values (4.0 and 9.2) resemble those of earlier compounds. Another type with a decreased incidence of drowsiness has the two nitrogen atoms of ethylenediamine joined by two saturated carbon atoms to give a piperazine ring. Chlorcyclizine 9.56a) ( Histantin , Diparalene ) provides an example. The search for Hi antagonists that could not cross the blood-brain barrier, and hence would be non-sedative, has produced the sterically-hindered astemizole ( Hismanol ) which is l-(p-fluorobenzyl)-2-[l-(l-/ methoxyphen-ethyl)-4-piperidylamino]benzimidazole, used for hay fever (Laduron et al., 1982). 

---